The Enhanced Liver Fibrosis test is associated with liver-related outcomes in postmenopausal women with risk factors for liver disease

Abstract

Background: Chronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit lifesaving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS).Methods: In a cohort of 95,126 we performed a case-control study measuring ELF in blinded samples from 173 participants with self-reported high alcohol use and / or BMI ≥25 kg/m 2 comprising all 58 cases who developed LRE and 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8.5 years.Results: Using Cox regression at an ELF threshold of 10.51 hazard ratios (HR) for LRE were 4.88 (95% confidence interval (CI) 2.37-10.03) (unadjusted model) and 4.62 (95% CI 2.12-10.08) (adjusted for deprivation and self-reported hypertension, heart disease, hypercholesterolaemia and diabetes). At a threshold of 9.8 HR for LRE were 2.21 (95% CI 1.22-3.97) (unadjusted model) and 2.18 (95% CI 1.19-4.01) (adjusted). ELF was evaluated as a time dependent variable by generating time-dependent Cox models; HRs at an ELF threshold of 10.51 were 1.94 (95% CI 1.10-3.39) (unadjusted) and 2.05 (95% CI 1.16-3.64) (adjusted) and at a threshold of 9.8 HRs were 1.85 (95% CI 1.09-3.15) (unadjusted) and 1.80 (95% CI 1.04-3.13) (adjusted). Area under the receiver operating characteristic curve for recruitment ELF predicting LRE was 0.58 (95% CI 0.49-0.68), and for second subsequent ELF 0.61 (95% CI 0.52-0.71). Conclusion:This study demonstrates the association between ELF and CLD in postmenopausal women with risk factors for liver disease, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the potential of ELF as a prognostic tool in health checks in primary care.(Continued on next page)

Enhanced liver Fibrosis® test predicts liver-related outcomes in the general population

“… 47 Another population-based case-control study (n = 173) comprising post-menopausal women with risk factors for liver disease found an AUC of 0.58 for liver-related outcomes. 48 …”

A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis

“…ELF measures 3 direct markers of liver fibrosis: hyaluronic acid (a glycosaminoglycan that is produced by hepatic stellate cells), PIIINP (a marker of early fibrogenesis and inflammation), and tissue inhibitor of matrix metalloproteinase 1 (the circulating inhibitor of MMP enzymes that can enhance fibrogenesis). Multiple studies have shown that ELF is predictive of hepatic decompensation, liver transplant, liver cancer, and death in chronic liver diseases, [26][27][28] and is superior to fibrosis-4 index, MELD score and Child-Pugh score for predicting the risk of liver-related events. [26] The incidence of hepatic events increased significantly with increased ELF, and lower ELF scores were associated with a reduced risk of liver-related outcomes.…”

Protective effect of phytoestrogens on nonalcoholic fatty liver disease in postmenopausal women

“…For example, in some clinical investigations, the prevalence of NAFLD was lower in premenopausal women than in men (12.7% vs. 26%), but considerably higher in postmenopausal women than in males of the same age (19.4% vs. 14.9%) (Lonardo et al, 2019;DiStefano, 2020). Furthermore, Trembling et al and Sumida et al confirmed that long-term estrogen deficiency may increase the risk of NAFLD fibrosis in postmenopausal women (Sumida et al, 2020;Trembling et al, 2020). Similarly, the ovariectomized (OVX) rodent models suggest a causal relationship between estrogen deficiency and increased susceptibility to NAFLD (Li et al, 2013;Jeong et al, 2018;Chang et al, 2020).…”